Hydrochloric Acid → Methyl 2-(3-(1-(tert-butoxycarbonyl) azetidin-3-ylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate

HRID 1801338Notes

Reaction equation

HRID 1801338 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18](O)=[O:19])[C:9]([CH3:25])([CH3:24])[CH2:8]2)=[O:4].ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.Cl.CN1CCOCC1.[NH2:55][CH:56]1[CH2:59][N:58]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:57]1>ClCCl>[C:63]([O:62][C:60]([N:58]1[CH2:57][CH:56]([NH:55][C:18]([C:17]2[CH:16]=[C:15]([CH:10]3[C:9]([CH3:25])([CH3:24])[CH2:8][C:7]4[C:12](=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=4)[NH:11]3)[CH:23]=[CH:22][CH:21]=2)=[O:19])[CH2:59]1)=[O:61])([CH3:66])([CH3:65])[CH3:64]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 674419763-(6-(Methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid

Product 1

HCID 67441328Methyl 2-(3-(1-(tert-butoxycarbonyl) azetidin-3-ylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylateYield 107.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(6-(methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid (150 mg, 0.44 mmol, 1.0 eq.) in dichloromethane (10.0 ml) was added N-hydroxy benzotriazole (89.2 mg, 0.66 mmol, 1.5 eq.) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.hydrochloric acid (253.0 mg, 1.32 mmol, 3.0 eq.), followed by 4-methylmorpholine (133.5 mg, 1.32 mmol) and the resultant mixture was stirred at room temperature for 30 min. Then tert-butyl 3-aminoazetidine-1-carboxylate (90.9 mg, 0.53 mmol, 1.2 eq.) was added to the flask and the reaction mixture was stirred for an additional 30 min. LC-MS showed the reaction was complete. The reaction was quenched with water, separated, and the aqueous layer was extracted with dichloromethane (twice). The combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and brine (3 times), dried over anhydrous magnesium sulfate. Removal of the solvent in vacuo gave 234 mg of methyl 2-(3-(1-(tert-butoxycarbonyl) azetidin-3-ylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate as a white solid, which was used in next step without further purification.

Workup

  1. customThe reaction was quenched with water
  2. customseparated
  3. extractionthe aqueous layer was extracted with dichloromethane (twice)
  4. washThe combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and brine (3 times)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-affa9e856583489eb6e6fc04e2ce1835
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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